Publications by authors named "Amir Kugelman"

91 Publications

FOREWORD.

Authors:
Amir Kugelman

Pediatr Pulmonol 2021 Jun;56 Suppl 2:S5

President, CIPP XX, 2021.

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http://dx.doi.org/10.1002/ppul.25495DOI Listing
June 2021

Respiratory morbidity in very low birth weight infants through childhood and adolescence.

Pediatr Pulmonol 2021 06 3;56(6):1609-1616. Epub 2021 Mar 3.

Department of Neonatology, Rambam Health Care Campus, Haifa, Israel.

Objective: To describe the long-term (up to 18 years of age) respiratory outcomes of children and adolescents born at very low birth weight (VLBW; ≤1500 g) in comparison with that of children born >1500 g.

Methods: An observational, longitudinal, retrospective study comparing VLBW infants with matched controls, registered at a large health maintenance organization in Israel. Pulmonary outcomes collected anonymously from the electronic medical files included respiratory illness diagnoses, purchased medications for respiratory problems, office visits with either a pediatric pulmonologist or cardiologist and composite respiratory morbidity combining all these parameters.

Results: Our study included 5793 VLBW infants and 11,590 matched controls born between 1998 and 2012. The majority (99%) of VLBW infants were premature (born < 37 weeks' gestation), while 93% of controls were born at term. The composite respiratory morbidity was significantly higher in VLBW infants compared with controls in all age groups (relative risk [95% confidence interval]: 1 year: 1.22 [1.19-1.26], <2 years: 1.30 [1.27-1.34], 2-6 years: 1.29 [1.27-1.32], 6-12 years: 1.53 [1.47-1.59], 12-18 years: 1.46 [1.35-1.56]; respectively). Both VLBW infants and controls demonstrated a steady decline in the composite respiratory morbidity with aging. In VLBW infants, lower gestational age was associated with higher respiratory morbidity only until 2 years of age and the morbidity declined in each gestational age group until adolescence.

Conclusion: Our study confirmed a strong association between VLBW and pulmonary morbidity. The higher prevalence of respiratory composite morbidity in VLBW infants persists over the years until adolescence. The respiratory morbidity is most evident in the first year of life and declines afterward.
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http://dx.doi.org/10.1002/ppul.25329DOI Listing
June 2021

Evaluation of audio-voice guided application for neonatal resuscitation: a prospective, randomized, pilot study.

J Perinat Med 2021 May 10;49(4):520-525. Epub 2020 Dec 10.

Department of Neonatology, Ruth Rapapport Children's Hospital, Rambam Health Care Campus, Haifa, Israel.

Objectives: To examine whether audio-voice guidance application improves adherence to resuscitation sequence and recommended time frames during neonatal resuscitation.

Methods: A prospective, randomized, pilot study examining the use of an audio-voice application for guiding resuscitation on newborn mannequins, based on the Neonatal Resuscitation Program (NRP) algorithm. Two different scenarios, with and without voice guidance, were presented to 20 medical personnel (2 midwives, 8 nurses, and 10 physicians) in random order, and their performance videotaped.

Results: Audio-voice guided resuscitation compared with non-guided resuscitation, resulted in significantly better compliance with NRP order sequence (p<0.01), correct use of oxygen supplementation (p<0.01) and performance of MR SOPA (Mask, reposition, suction, open mouth, pressure, airway) (p<0.01), and shortened the time to "positive pressure ventilation" (p<0.01).

Conclusions: In this pilot study, audio-voice guidance application for newborn resuscitation simulation on mannequins, based on the NRP algorithm, improved adherence and performance of NRP guidelines.
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http://dx.doi.org/10.1515/jpm-2020-0173DOI Listing
May 2021

Cannula With Long and Narrow Tubing vs Short Binasal Prongs for Noninvasive Ventilation in Preterm Infants: Noninferiority Randomized Clinical Trial.

JAMA Pediatr 2021 Jan;175(1):36-43

Rambam Medical Center & Rapport Faculty of Medicine, Haifa, Israel.

Importance: Use of cannulas with long and narrow tubing (CLNT) has gained increasing popularity for applying noninvasive respiratory support for newborn infants thanks to ease of use, perceived patient comfort, and reduced nasal trauma. However, there is concern that this interface delivers reduced and suboptimal support.

Objective: To determine whether CLNT is noninferior to short binasal prongs and masks (SPM) when providing nasal intermittent positive pressure ventilation (NIPPV) in preterm infants.

Design, Setting, And Participants: This randomized controlled, unblinded, prospective noninferiority trial was conducted between December 2017 and December 2019 at 2 tertiary neonatal intensive care units. Preterm infants born between 24 weeks' and 33 weeks and 6 days' gestation were eligible if presented with respiratory distress syndrome with the need for noninvasive ventilatory support either as initial treatment after birth or after first extubation. Analysis was performed by intention to treat.

Interventions: Randomization to NIPPV with either CLNT or SPM interface.

Main Outcomes And Measures: The primary outcome was the need for intubation within 72 hours after NIPPV treatment began. Noninferiority margin was defined as 15% or less absolute difference.

Results: Overall, 166 infants were included in this analysis, and infant characteristics and clinical condition (including fraction of inspired oxygen, Pco2, and pH level) were comparable at recruitment in the CLNT group (n = 83) and SPM group (n = 83). The mean (SD) gestational age was 29.3 (2.2) weeks vs 29.2 (2.5) weeks, and the mean (SD) birth weight was 1237 (414) g vs 1254 (448) g in the CLNT and SPM groups, respectively. Intubation within 72 hours occurred in 12 of 83 infants (14%) in the CLNT group and in 15 of 83 infants (18%) in the SPM group (risk difference, -3.6%; 95% CI, -14.8 to 7.6 [within the noninferiority margin], χ2 P = .53). Moderate to severe nasal trauma was significantly less common in the CLNT group compared with the SPM group (4 [5%] vs 14 [17%]; P = .01). There were no differences in other adverse events or in the course during hospitalization.

Conclusions And Relevance: In this study, CLNT was noninferior to SPM in providing NIPPV for preterm infants, while causing significantly less nasal trauma.

Trial Registration: ClinicalTrials.gov Identifier: NCT03081611.
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http://dx.doi.org/10.1001/jamapediatrics.2020.3579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653541PMC
January 2021

[ALTERATIONS IN SENSITIVE MEASURES OF CARDIAC FUNCTION IN HEALTHY NEONATES DURING PHOTOTHERAPY].

Harefuah 2020 Oct;159(10):739-744

Rappaport Faculty of Medicine, Technion- Israel Institute of Technology, Haifa, Israel.

Objectives: Phototherapy has been reported to reduce coronary blood flow in neonates but without affecting gross measures of cardiac function. The aim of our current study was to evaluate earlier, more sensitive changes in cardiac function during phototherapy.

Methods: Nineteen neonates with jaundice treated with phototherapy had Doppler echocardiographic evaluation, before, during and after phototherapy and were compared to 25 matched controls. Sensitive measures for cardiac performance in this study included left ventricular dimension, ventricular Doppler parameters and regional function assessment.

Results: Phototherapy was associated with a significant increase in heart rate. In addition, atrioventricular valve closure to opening interval decreased significantly during phototherapy while ventricular ejection times tended to decrease. However, left and right ventricular filling parameters and outflow velocity parameters, longitudinal tissue-Doppler annular velocities and myocardial performance indices were not affected by phototherapy and were similar to those in controls. Coronary blood velocities and integrals decreased significantly during phototherapy.

Conclusions: Our study found no differences in early and sensitive measures of cardiac performance including the diastolic and systolic function, despite modestly lower flow in coronary arteries among healthy neonates during phototherapy.
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October 2020

Ductal steal: does it affect pre-ductal arteries.

J Perinatol 2021 01 6;41(1):4-5. Epub 2020 Oct 6.

Department of Neonatology, Rambam Medical Center, Rappaport Faculty of Medicine, Haifa, Israel.

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http://dx.doi.org/10.1038/s41372-020-00844-3DOI Listing
January 2021

Antenatal betamethasone and the risk of neonatal hypoglycemia: it's all about timing.

Arch Gynecol Obstet 2021 03 22;303(3):695-701. Epub 2020 Sep 22.

Department of Obstetrics and Gynecology, Rambam Health Care Campus, 3109601, Haifa, Israel.

Introduction: Our objective was to evaluate whether there is a relationship between the "time during the day" of maternal betamethasone administration between 24 and 34 weeks' gestation and the risk for neonatal hypoglycemia.

Material And Methods: A retrospective study included cases between 2008 and 2018. Eligible cases were pregnant women with singleton pregnancies who received a single course of betamethasone between 24 and 34 weeks' gestation. Each woman was allocated into one of four pre-defined groups based on the time when intramuscular betamethasone was administered. Group 1 (23:00-04:59) represents the lowest daily natural corticosteroids' activity, group 2 (05:00-10:59) represents the peak daily natural corticosteroids' activity, whereas group 3 (11:00-16:59) and group 4 (17:00-22:59) present an intermediate natural state of steady corticosteroids' secretion and activity. The primary outcome of the study was the incidence of neonatal hypoglycemia (glucose level of less than 40 mg/dL).

Results: We have identified 868 women who received a single complete course of betamethasone, of which 353 women (40.7%) had a steroid treatment latency to delivery up to 14 days. The incidence of neonatal hypoglycemia was significantly higher in group 2 (39.5%, 30/76, p = 0.0063), compared to group 1, who had the lowest incidence of neonatal hypoglycemia (16.9%, 12/71), and to group 3 and group 4.

Conclusions: The "time during the day" when betamethasone administered is important when considering the risk for neonatal hypoglycemia. The risk was significantly higher when betamethasone was administered during the peak time and significantly lower when administered at the nadir time of maternal endogenous corticosteroid activity.
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http://dx.doi.org/10.1007/s00404-020-05785-yDOI Listing
March 2021

High-flow nasal cannula therapy: can it be recommended as initial or rescue care for infants with moderate bronchiolitis in the paediatric ward?

Authors:
Amir Kugelman

Eur Respir J 2020 07 16;56(1). Epub 2020 Jul 16.

Dept of Neonatology and Pediatric Pulmonary Unit, Rambam Medical Center, Rappaport Faculty of Medicine, Technion, Haifa, Israel

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http://dx.doi.org/10.1183/13993003.01020-2020DOI Listing
July 2020

Oxygenation Instability Assessed by Oxygen Saturation Histograms during Supine vs Prone Position in Very Low Birthweight Infants Receiving Noninvasive Respiratory Support.

J Pediatr 2020 Jun 29. Epub 2020 Jun 29.

Neonatal Intensive Care Unit, Ruth Rappaport Children's Hospital, Rambam Health Campus, Haifa, Israel; Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. Electronic address:

Objective: To evaluate the effect of prone vs supine position on the oxygenation instability among very low birth weight (VLBW) infants receiving noninvasive respiratory support, as assessed by the average oxygen saturation (SpO) histograms.

Study Design: Sixty-nine histograms from 23 VLBW infants were studied prospectively. Each infant was studied during 3 consecutive 3-hour periods of alternating positions; 12 infants started the study while prone and 11 infants started supine, by random order. Histogram classification system was used to quantify oxygenation stability and time spent in different SpO ranges.

Results: The fraction of inspired oxygen values were similar in both positions. Unstable histograms were more common in supine vs prone position (20/34 [59%] vs 10/35 [29%]; P = .02, respectively). Analyzing oxygenation stability as per position change revealed that a change from prone to supine increased oxygenation instability, and supine to prone decreased instability (P = .02). In the supine vs prone position, percent of time spent in SpO ≤80% and <90% was higher (5.0 ± 4.2 vs 2.4 ± 3.4 [P < .001] and 24.1 ± 13.7 vs 13.2 ± 10.0 [P < .001], respectively), and percent of time in SpO >94% was lower (39.7 ± 26.0 vs 52.4 ± 23.4 [P = .04]).

Conclusions: Prone positioning decreased oxygenation instability and resulted in higher oxygenation among VLBW premature infants on noninvasive respiratory support. SpO histograms allow easy bedside assessment of oxygenation instability, and quantification of the time spent at different SpO ranges.
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http://dx.doi.org/10.1016/j.jpeds.2020.06.066DOI Listing
June 2020

The effect of patent ductus arteriosus on coronary artery blood flow in premature infants: a prospective observational pilot study.

J Perinatol 2020 09 20;40(9):1366-1374. Epub 2020 Feb 20.

Department of Neonatology, Rambam Medical Center, Rappaport Faculty of Medicine, Haifa, Israel.

Objective: To compare coronary flows between premature infants with and without hemodynamically significant patent ductus arteriosus (hsPDA) and to determine if coronary flow is influenced by medical PDA treatment.

Design: Prospective, observational pilot study. Forty-three infants <32 weeks gestation underwent echocardiography when routinely indicated. Study group included infants with hsPDA requiring treatment. Comparison groups included infants with nonsignificant PDA and infants without PDA.

Results: The study group (n = 13), compared with the comparison groups with nonsignificant PDA (n = 12) and without PDA (n = 18) had higher troponin levels (p = 0.003 and 0.004, respectively). In infants with hsPDA compared with infants with no PDA there was a significant increase in myocardial oxygen demand and decrease in left main coronary artery flow, with nonsignificant increase in cardiac output.

Conclusions: Decrease in coronary artery flows and higher troponin values may suggest a "steal effect," not allowing to meet the elevated myocardial oxygen demand in infants with hsPDA.
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http://dx.doi.org/10.1038/s41372-020-0622-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222133PMC
September 2020

Neonatal frontal lobe: sonographic reference values and suggested clinical use.

Pediatr Res 2020 02 10;87(3):536-540. Epub 2019 Oct 10.

Research Unit, Nazareth Hospital, Nazareth, Israel.

Background: Intraventricular hemorrhage (IVH) and post-hemorrhagic hydrocephalus (PHHC) remain major problems among premature infants. The need, timing and type of ventricular drainage are based on sonographic ventricular measures, without assessment of the dimensions of the frontal lobe. The aim of our study was to establish new reference values for sonographic frontal lobe cortico-ventricular thickness (FL-CVT) in a large cohort of infants.

Methods: All normal head ultrasound scans that were performed in our center during the first 4 days of life between January 2014 and December 2016 were retrospectively evaluated.

Results: Scans were evaluated and plotted to create a reference range for the thickness of the frontal lobe in normal infants of 24-40 weeks' gestation. The FL-CVT increased significantly during gestation. Calculating the area under the curve of the FL-CVT in 9 infants with post-hemorrhagic-hydrocephalus (PHHC) reveals a 20% mean loss of FL-CVT. The impact of increasing ventricular dilatation and of the various ventricular drainage procedures on the frontal lobe growth were described in two infants demonstrating the potential clinical value of this tool.

Conclusions: Head ultrasound provides a simple, non-invasive method for measuring the thickness of the frontal lobe, which grows significantly between 24 and 40 weeks' gestation. In premature infants with PHHC, we suggest the use of the FL-CVT measure, in addition to ventricular size measures, as a direct assessment of the impact of the enlarged ventricles on the surrounding brain parenchyma. This could assist in the management of PHHC and determine the need and optimal timing for intervention.
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http://dx.doi.org/10.1038/s41390-019-0605-3DOI Listing
February 2020

Abdominal aortic perforation by an umbilical arterial catheter.

Arch Dis Child Fetal Neonatal Ed 2020 Jan 29;105(1):40. Epub 2019 Aug 29.

Neonatology, Rambam Health Care Campus, Haifa, Israel.

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http://dx.doi.org/10.1136/archdischild-2019-317869DOI Listing
January 2020

Continuous Noninvasive Carbon Dioxide Monitoring in Neonates: From Theory to Standard of Care.

Pediatrics 2019 07;144(1)

Department of Neonatology, Rambam Health Care Campus, Haifa, Israel; and.

Ventilatory support may affect the short- and long-term neurologic and respiratory morbidities of preterm infants. Ongoing monitoring of oxygenation and ventilation and control of adequate levels of oxygen, pressures, and volumes can decrease the incidence of such adverse outcomes. Use of pulse oximetry became a standard of care for titrating oxygen delivery, but continuous noninvasive monitoring of carbon dioxide (CO) is not routinely used in NICUs. Continuous monitoring of CO level may be crucial because hypocarbia and hypercarbia in extremely preterm infants are associated with lung and brain morbidities, specifically bronchopulmonary dysplasia, intraventricular hemorrhage, and cystic periventricular leukomalacia. It is shown that continuous monitoring of CO levels helps in maintaining stable CO values within an accepted target range. Continuous monitoring of CO levels can be used in the delivery room, during transport, and in infants receiving invasive or noninvasive respiratory support in the NICU. It is logical to hypothesize that this will result in better outcome for extremely preterm infants. In this article, we review the different noninvasive CO monitoring alternatives and devices, their advantages and disadvantages, and the available clinical data supporting or negating their use as a standard of care in NICUs.
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http://dx.doi.org/10.1542/peds.2018-3640DOI Listing
July 2019

Experience with intramuscular glucagon for infants with early neonatal hypoglycemia.

J Pediatr Endocrinol Metab 2019 Sep;32(9):1023-1026

Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.

Parenteral options for treating neonatal hypoglycemia (NH) include: intramuscular (i.m.) glucagon or intravenous (i.v.) glucose 10%. So far, the role of i.m. glucagon in treating NH has not been adequately assessed. We retrospectively studied 236 neonates with NH. One hundred and twenty-one infants received oral glucose-fortified-milk-based formula (OGFM) and their blood glucose level (BGL) was maintained thereafter. Two groups of infants required intervention: (a) OGFM + i.m. glucagon (n = 77, 32.6%) and (b) OGFM + i.v. glucose bolus (n = 38, 16.1%). BGL1, BGL2 and BGL3 denote pre-treatment BGL, 2-2.5 h post-treatment and BGL within 2.5-4 h post-treatment; respectively. The two groups were compared regarding two outcome measures: Outcome no. 1: BGL2 ≥ 45 mg/dL and outcome no. 2: BGL3 ≥ 45 mg/dL. Compared to i.v. glucose, the i.m. glucagon group had significantly more infants with BGL2 ≥ 45 mg/dL (40% vs. 76%, p = 0.028), and marginal significant difference regarding BGL3 ≥ 45 mg/dL (62% vs. 77%, p = 0.08). Univariate analysis showed that i.m. glucagon, male gender, vacuum extraction, cesarean delivery and one or more NH risk factors were significantly associated with outcome measure no. 1. I.m. glucagon, small for gestational age status, cesarean delivery, BGL1 and NH risk factors were associated with outcome measure no. 2. Multi-variate analysis showed that i.m. glucagon was significantly and independently associated with BGL2 ≥ 45 mg/dL. I.m. glucagon is worth consideration as a treatment option for NH.
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http://dx.doi.org/10.1515/jpem-2018-0562DOI Listing
September 2019

Effect of late preterm birth on lung clearance index and respiratory physiology in school-age children.

Pediatr Pulmonol 2019 08 15;54(8):1250-1256. Epub 2019 May 15.

Pediatric Pulmonary Institute and CF Center, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel.

Background: We hypothesized that former late preterm (LP) children have abnormal pulmonary physiology parameters, including uneven ventilation distribution, due to premature disruption of normal lung development.

Methods: A cross-sectional study evaluating former LP children at the age of 6 to 12 years as compared to term controls. Demographics and child's and family history of asthma/atopy/smoking were recorded. The outcome parameters were spirometry, multiple breath washout (MBW) measurement by lung clearance index (LCI), 6-minute walk test (6MWT), symptoms related to asthma and allergy, and Godin Leisure-Time Exercise Questionnaire.

Results: Twenty-nine former LP were compared to 30 term-control children (mean age, 8.2 ± 1.7 and 8.8 ± 1.8 years, respectively). LP had reduced forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) compared to term controls (FEV1 1.59 ± 0.48 vs 1.80 ± 0.39 L, P = 0.005 and FVC 1.73 ± 0.45 vs 1.99 ± 0.49 L, P = 0.009). There were no differences between the two groups regarding FEV1/FVC, forced expiratory flow between 25 and 75 (FEF25-75), LCI (7.10 ± 0.79 vs 6.96 ± 0.75, P = 0.50), 6MW distance, and weekly leisure-activity score. Former LP children had more episodes of wheezing and greater use of asthma medication.

Conclusions: This pilot study suggests that LP have lower pulmonary function tests (PFTs) but not ventilation inhomogeneity measured by LCI or functional disturbance. It is unclear if the differences in PFTs are due to late prematurity by itself or are the consequence of maternal and neonatal factors associated with LP. Further larger studies are required to assess the long-term respiratory consequences of LP birth.
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http://dx.doi.org/10.1002/ppul.24357DOI Listing
August 2019

Expert consensus on palivizumab use for respiratory syncytial virus in developed countries.

Paediatr Respir Rev 2020 Feb 18;33:35-44. Epub 2018 Dec 18.

Neonatology Service, Hospital Clinic, Institut d'Investigacions Biomediques August Pi Suñer (IDIBAPS), Carrer del Rosselló 149, 08036 Barcelona, Spain. Electronic address:

Respiratory syncytial virus (RSV) infection is a leading cause of hospitalisation in early childhood and palivizumab is the only licensed intervention for prevention. Palivizumab guidelines should reflect the latest evidence, in addition to cost-effectiveness and healthcare budgetary considerations. RSV experts from Europe, Canada and Israel undertook a systematic review of the evidence over the last 5 years and developed recommendations regarding prophylaxis in industrialised countries. Almost 400 publications were reviewed. This group recommended palivizumab for: preterm infants (<29 and ≤31 weeks gestational age [wGA] and ≤9 and ≤6 months of age, respectively; high-risk 32-35wGA), former preterm children ≤24 months with chronic lung disease/bronchopulmonary dysplasia, children ≤24 months with significant congenital heart disease; and other high-risk populations, such as children ≤24 months with Down syndrome, pulmonary/neuromuscular disorders, immunocompromised, and cystic fibrosis. Up to 5 monthly doses should be administered over the RSV season. It is our impression that the adoption of these guidelines would help reduce the burden of RSV.
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http://dx.doi.org/10.1016/j.prrv.2018.12.001DOI Listing
February 2020

Respiratory Viruses Frequently Mimic Pertussis in Young Infants.

Pediatr Infect Dis J 2019 05;38(5):e107-e109

Clinical Microbiology Laboratory, Bnai Zion Medical Center, Haifa, Israel.

Bordetella pertussis is prevalent among infants, but its diagnosis is complicated by the fact that its signs and symptoms overlap with respiratory viruses. Indeed, when evaluating the etiology of infants less than 1 year of age suspected of having pertussis, we found that respiratory viruses frequently mimic B. pertussis and are more likely to be the causative agent.
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http://dx.doi.org/10.1097/INF.0000000000002223DOI Listing
May 2019

Long term follow-up of Palivizumab administration in children born at 29-32 weeks of gestation.

Respir Med 2019 04 19;150:149-153. Epub 2019 Mar 19.

Pediatric Pulmonary Institute, Ruth Children's Hospital, Rambam Health Care Campus, Haifa, Israel; The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. Electronic address:

Background: Severe respiratory syncytial virus (RSV) bronchiolitis requiring hospitalization induces long term immunological and respiratory abnormalities. The long-term immunomodulation effect of Palivizumab (RSV monoclonal antibody) prophylaxis and its impact on the development of asthma remain controversial. Our aim was to evaluate airway hyper-reactivity, systemic inflammatory markers, allergic parameters and respiratory morbidity, 5-7 years following Palivizumab administration to children born at 29-32 weeks of gestation (WGA).

Methods: Children born at 29-32 WGA were evaluated at age 5-7 years. Methacholine challenge test (MCT), serum inflammatory cytokines, fractional exhaled nitric oxide (FeNO), blood tests for eosinophil count, IgE and assessment of respiratory morbidity by questionnaire were compared between those born before Palivizumab prophylaxis was extended to 29-32 WGA and those who received Palivizumab prophylaxis.

Results: Of 42 children recruited, 27 received Palivizumab and 15 did not. The mean gestational age and weight were lower in the Palivizumab group. Similar values of spirometry, MCT, FeNO and allergic parameters were observed in the two groups. The Palivizumab group had higher IL4, IL5 and IL13 (Th2 cytokines), IL6, IL17α, and G-CSF (Th17 activation), and lower IL12 and higher INF-γ (Th1 cytokines).

Conclusion: Compared to children who did not receive immunoprophylaxis, among children who received Palivizumab, no beneficial effects on long-term respiratory morbidity, airway reactivity or allergic parameters were observed, and levels of Th2 and Th17 cytokines implicated in the pathogenesis of asthma were higher. These findings cast doubt on the potential long-term beneficial effect of Palivizumab on asthma inception.
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http://dx.doi.org/10.1016/j.rmed.2019.03.001DOI Listing
April 2019

Three-step management of a newborn with a giant, highly vascularized, cervical teratoma: a case report.

J Med Case Rep 2019 Mar 10;13(1):73. Epub 2019 Mar 10.

Neonatal Intensive Care Unit, Ruth Rappaport Children's Hospital, Rambam Health Campus, Haifa, Israel.

Background: A giant congenital cervical teratoma is often highly vascularized; thus, in addition to a life-threatening airway occlusion at birth it comprises a high risk for significant and lethal blood loss during resection. In the case presented, an endovascular embolization of the carotid artery that supplied a giant congenital cervical teratoma was done as part of a three-stage treatment soon after birth and contributed to an overall good outcome. Embolization in cases of cervical teratomas was not described previously.

Case Presentation: We present a case of a preterm newborn from a Sephardic jewish origin with a giant, highly vascularized, congenital cervical teratoma that was managed successfully in three stages: (1) delivery by an ex utero intrapartum treatment procedure after extensive preoperative planning and followed by tracheostomy, (2) endovascular embolization of the carotid artery that supplied the tumor in order to decrease blood loss during resection, and (3) complete surgical resection. The parents were involved in all the ethical and medical decisions, starting just after the cervical mass was diagnosed prenatally.

Conclusion: The management of giant congenital cervical teratoma is often challenging from both a medical and ethical prospective. Meticulous perinatal planning and parents' involvement is crucial. Endovascular embolization of the tumor feeding vessels can significantly improve the resection outcome and overall prognosis.
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http://dx.doi.org/10.1186/s13256-019-1976-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409158PMC
March 2019

Induction of labor versus expectant management among women with macrosomic neonates: a retrospective study.

J Matern Fetal Neonatal Med 2020 Jun 2;33(11):1831-1839. Epub 2018 Dec 2.

Department of Obstetrics and Gynecology, Bnai-Zion Medical Center, Israel Affiliated to the Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.

The macrosomic fetus predisposes a variety of adverse maternal and perinatal outcomes. Although older studies have shown no benefit in inducing women of suspected macrosomic fetuses, more updated studies show different information. The aim of our study was to compare induction of labor versus expectant management among women with macrosomic neonates weighing more than 4000 g at term (between 37° and 41 weeks' gestation). This was a retrospective cohort study of all live-born singleton pregnancies with macrosomic newborns who were delivered at our institution between 1 January 2000 and 1 June 2015. We compared the outcomes of induction of labor, at each gestational age (GA), between 37 and 41 weeks (study group) with ongoing pregnancy. The primary outcome was cesarean section (CS) rate. Secondary outcomes were composite maternal and neonatal outcome and birth injuries. Overall, out of 3095 patients with macrosomic newborns who were included in the study, 795 women (25.7%) underwent induction of labor. The cesarean section rate was not found to be significantly different between the groups at all gestational ages, nor was the vaginal delivery rate. After adjusting for confounders, induction of labor at 40 and 41 weeks' gestation was associated with composite maternal outcome (adjusted odds ratio (aOR) 1.6, 95% confidence interval (CI): 1.3-2.1; aOR 1.7, 95% CI: 1.3-2.2, respectively) and composite neonatal outcome (aOR 1.6, 95% CI: 1.1-2.4; aOR 1.8, 95% CI: 1.1-2.9). Induction of labor at 40 weeks' gestation was also associated with increased risk of birth injuries (aOR 2.9, 95% CI: 1.4-6). Compared with ongoing pregnancy, induction of labor of women with macrosomic neonates between 37 and 41 weeks of gestation does not reduce the CS rate, nor does it increase the vaginal delivery rate. Moreover, induction of labor of those women beyond 39 weeks' gestation is associated with composite adverse maternal/neonatal outcome, specifically birth injuries.
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http://dx.doi.org/10.1080/14767058.2018.1531121DOI Listing
June 2020

Less is More: Modern Neonatology.

Rambam Maimonides Med J 2018 Jul 30;9(3). Epub 2018 Jul 30.

Department of Neonatology, Rambam Health Care Campus, Haifa, Israel.

Iatrogenesis is more common in neonatal intensive care units (NICUs) because the infants are vulnerable and exposed to prolonged intensive care. Sixty percent of extremely low-birth-weight infants are exposed to iatrogenesis. The risk factors for iatrogenesis in NICUs include prematurity, mechanical or non-invasive ventilation, central lines, and prolonged length of stay. This led to the notion that "less is more." In the delivery room delayed cord clamping is recommended for term and preterm infants, and suction for the airways in newborns with meconium-stained fluid is not performed anymore. As a symbol for a less aggressive attitude we use the term neonatal stabilization rather than resuscitation. Lower levels of oxygen saturations are accepted as normal during the first 10 minutes of life, and if respiratory assistance is needed, we no longer use 100% oxygen but 0.21-0.3 FiO, depending on gestational age and the level of oxygen saturation. We try to avoid endotracheal ventilation by using non-invasive respiratory support and administering continuous positive airway pressure early on, starting in the delivery room. If surfactant is needed, non-invasive methods of surfactant administration are utilized. Use of central lines is shortened, and early feeding of human milk is the routine. Permissive hypercapnia is allowed, and continuous non-invasive monitoring not only of the O but also of CO is warranted. "Kangaroo care" and Newborn Individualized Developmental Care and Assessment Program (NIDCAP) together with a calm atmosphere with parental involvement are encouraged. Whether "less is more," or not enough, is to be seen in future studies.
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http://dx.doi.org/10.5041/RMMJ.10344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115478PMC
July 2018

Adding Paracetamol to Ibuprofen for the Treatment of Patent Ductus Arteriosus in Preterm Infants: A Double-Blind, Randomized, Placebo-Controlled Pilot Study.

Am J Perinatol 2018 11 21;35(13):1319-1325. Epub 2018 May 21.

Neonatal Intensive Care Unit, Ruth Rappaport Children's Hospital, Rambam Health Campus, Rappoart Faculty of Medicine, Technion, Haifa, Israel.

Objective: The objective of this study was to compare the closure rate of hemodynamically significant patent ductus arteriosus (hsPDA) of intravenous ibuprofen + paracetamol (acetaminophen) versus ibuprofen + placebo, in preterm infants of 24 to 31 weeks postmenstrual age.

Study Design: This is a single-center, double-blind, randomized controlled pilot study. Infants were assigned for treatment with either intravenous ibuprofen + paracetamol ( = 12) or ibuprofen + placebo ( = 12).

Results: There was no statistical difference in baseline characteristics of the two groups. Echocardiography parameters were comparable before treatment in both groups. There was a trend toward higher hsPDA closure rate in the paracetamol group in comparison to the placebo group (83 vs. 42%,  = 0.08). No adverse effects, clinical or laboratory, were associated with adding paracetamol.

Conclusion: Our pilot study was unable to detect a beneficial effect by adding intravenous paracetamol to ibuprofen for the treatment of hsPDA. Larger prospective studies are needed to explore the positive tendency suggested by our results and to assure safety.
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http://dx.doi.org/10.1055/s-0038-1653946DOI Listing
November 2018

Optimizing Accessibility of a Hand-wash Gel to Infant's Cradle: Effect on Neonatal Conjunctivitis.

Pediatr Infect Dis J 2019 01;38(1):e7-e11

Department of Neonatology.

Background: In our recent study in 2015, we showed a significant relationship between increased rate of clinical neonatal conjunctivitis (CNC) and performance of eye red reflex examination. Our study aim was to assess whether improved accessibility of staff to disinfectant gel (via attaching the gel bottle to infant's cradle) will increase the caring staff compliance with hand hygiene and decrease the rate of CNC.

Methods: Our intervention included attaching bottles of alcohol-based gel to newborns' cradles to ensure full availability and accessibility of hand-wash disinfectant. We included all newborn infants who were born beyond 35 weeks' gestation and stayed in the well-baby nursery. We compared 2 periods: pre-intervention period (n = 9380) versus an intervention period (n = 8087). Three variables were recorded: (1) rate of CNC: number of conjunctival swabs sampled per 1000 newborns whenever an eye discharge was noted, (2) rate of bacterial conjunctivitis: number of positive swabs per 1000 newborns and (3) percentage of positive swabs out of all sampled swabs.

Results: Compared with pre-intervention period, the rate of CNC dropped significantly during the intervention period: 28.6/1000 versus 21.3/1000, respectively, P < 0.01. However, the number of positive bacterial swabs per 1000 newborns (3.2 vs. 2.5) and the percentage of positive bacterial swabs of all sent samples (11.6% vs. 10.8%) were not different between the 2 periods. The majority of pathogens in swabs were Gram-negative sp. without difference between study periods (77.4% vs. 80%), respectively. Univariate analysis showed significant association between rate of CNC and longer length of stay >5 days (P < 0.001) and vaginal delivery. Logistic stepwise regression analysis showed that 4 variables were significantly and independently associated with higher rate of clinical conjunctivitis. These include birth during pre-intervention period [P = 0.018, odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.04-1.54], length of stay 4-5 days (P < 0.001, OR = 2.23, CI: 1.63-3.06), length of stay >7 days (P < 0.001, OR = 6.51, CI: 4.24-10.02), vaginal delivery (P = 0.004, OR = 1.6, CI: 1.17-2.2) and male gender (P = 0.006, OR = 1.31, CI: 1.08-1.59).

Conclusions: Accessibility of a disinfectant gel within each newborn's cradle raised hygiene awareness among the caring staff and contributed to the reduction of CNC rate in the newborn nursery.
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http://dx.doi.org/10.1097/INF.0000000000002023DOI Listing
January 2019

Ventilation in Preterm Infants and Lung Function at 8 Years.

Authors:
Amir Kugelman

N Engl J Med 2017 10;377(16):1599

Rambam Medical Center, Haifa, Israel

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http://dx.doi.org/10.1056/NEJMc1711170DOI Listing
October 2017

Inhaled corticosteroids in transient tachypnea of the newborn: A randomized, placebo-controlled study.

Pediatr Pulmonol 2017 08 3;52(8):1043-1050. Epub 2017 Jul 3.

The B&R Rappaport Faculty of Medicine, Neonatology, Rambam Medical Center, Technion, Haifa, Israel.

Objective: Prenatal corticosteroids were shown to reduce the respiratory complication in late preterm infants. Our objective was to determine if early inhaled corticosteroids could alleviate the respiratory distress and morbidity in late preterm and term neonates with transient tachypnea of the newborn (TTN).

Study Design: Double-blind, randomized placebo-controlled, multicenter pilot study. Infants born at >34 weeks gestational age with TTN at 4 h of age were randomized to two doses, 12 h apart, of inhaled Budesonide 1000 μg/dose or placebo within 6 h from delivery. Analysis was done by intention to treat.

Results: The study (n = 24) and control (n = 25) groups were comparable in birth characteristics (gestational age: 36.8 ± 1.9 vs 36.4 ± 1.8 weeks) and clinical condition at the time of recruitment (vital signs, clinical score, ventilation support, and blood gases). There was no difference between the study and control groups in clinical score (based on grunting, retractions, ala nasi, and respiratory rate) at recruitment and at 12, 24, and 48 h after the first inhalation (4.3 ± 1.6 vs 4.1 ± 2.1; 1.9 ± 1.8 vs 1.5 ± 1.7; 1.1 ± 1.4 vs 1.3 ± 1.6; 0.5 ± 0.8 vs 0.6 ± 1.0; respectively). Respiratory support at each time point, time to spontaneous unsupported breathing (67.4 ± 74.1 vs 75.2 ± 95.2 h), time to full feeds (86.7 ± 68.7 vs 84.3 ± 66.6 h) and length of stay (9.9 ± 5.5 vs 12.4 ± 8.0 days) did not differ between the groups. We did not detect any side effects.

Conclusions: Our pilot study was unable to detect a beneficial effect of early administration of inhaled steroids on the clinical course of TTN in late preterm and term infants.
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http://dx.doi.org/10.1002/ppul.23756DOI Listing
August 2017

The Impact of Routine Evaluation of Gastric Residual Volumes on the Time to Achieve Full Enteral Feeding in Preterm Infants.

J Pediatr 2017 10 16;189:128-134. Epub 2017 Jun 16.

Department of Neonatology, Bnai Zion Medical Center, Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.

Objective: To evaluate the time to full enteral feedings in preterm infants after a practice change from routine evaluation of gastric residual volume before each feeding to selective evaluation of gastric residual volume , and to evaluate the impact of this change on the incidence of necrotizing enterocolitis (NEC).

Study Design: Data were collected on all gavage-fed infants born at ≤34 weeks gestational age (GA) for 2 years before (n = 239) and 2 years after the change (n = 233).

Results: The median GA was 32.0 (IQR: 29.7-33.0) weeks before and 32.4 (30.4-33.4) weeks after the change (P = .02). Compared with historic controls, infants with selective evaluations of gastric residual volumes weaned from parenteral nutrition 1 day earlier (P < .001) and achieved full enteral feedings (150 cc/kg/day) 1 day earlier (P = .002). The time to full oral feedings and lengths of stay were similar. The rate of NEC (stage ≥ 2) was 1.7% in the selective gastric residual volume evaluation group compared with 3.3% in the historic control group (P = .4). Multiple regression analyses showed that the strongest predictor of time to full enteral feedings was GA. Routine evaluation of gastric residual volume and increasing time on noninvasive ventilation both prolonged the attainment of full enteral feedings. Findings were consistent in the subgroup with birth weights of <1500 g. Increased weight at discharge was most strongly associated with advancing postmenstrual, age but avoidance of routine evaluations of gastric residual volume also was a significant factor.

Conclusions: Avoiding routine evaluation of gastric residual volume before every feeding was associated with earlier attainment of full enteral feedings without increasing risk for NEC.
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http://dx.doi.org/10.1016/j.jpeds.2017.05.054DOI Listing
October 2017

Population-based study on antenatal corticosteroid treatment in preterm small for gestational age and non-small for gestational age twin infants.

J Matern Fetal Neonatal Med 2018 Mar 28;31(5):553-559. Epub 2017 Feb 28.

b Ruth and Bruce Rappaport Faculty of Medicine , Technion-Israel Institute of Technology , Haifa , Israel.

Objectives: To assess the associations between antenatal corticosteroid use (ACU), mortality and severe morbidities in preterm, twin neonates and compare these between small for gestational age (SGA) and non-SGA twins.

Materials And Methods: Population-based study using data collected by the Israel National Very Low Birth Weight infant database from 1995 to 2012, comprising twin infants of 24-31 weeks' gestation, without major malformations. Univariate and multivariable logistic regression analyses were performed.

Results: Among the 6195 study twin infants, 784 were SGA. Among SGA neonates, ACU were associated with decreased mortality (23.9% vs. 39.2%, p < 0.0001) and composite adverse outcome including mortality or severe neonatal morbidity (43.8% vs. 56.8%, p = 0.0015), similar to the effect in non-SGA neonates (mortality 13.0% vs. 24.5%, p < 0.0001; composite outcome 34.2% vs. 44.8%, p < 0.0001). In the multivariable logistic regression analyses, ACU were associated with an almost 50% reduced mortality risk among SGA twin neonates (OR = 0.52, 95% CI 0.31-0.88) similar to the effect in non-SGA twin neonates (OR = 0.56, 95% CI 0.45-0.70), P = 0.69. Composite adverse outcome risk was also reduced in SGA (OR = 0.78, 95% CI 0.50-1.23) and non-SGA groups (OR = 0.78, 95% CI 0.65-0.95), P = 0.95.

Conclusions: ACU should be considered in all mothers with twin gestation, at risk for preterm delivery at 24-31 weeks, in order to improve perinatal outcome.
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http://dx.doi.org/10.1080/14767058.2017.1292242DOI Listing
March 2018

High flow nasal cannula and poor outcomes?

J Pediatr 2016 11 20;178:308. Epub 2016 Jun 20.

Department of Neonatology and Pediatric Pulmonary Unit Bnai Zion Medical Center The Ruth and Bruce Rappaport Faculty of Medicine Technion, Haifa, Israel.

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http://dx.doi.org/10.1016/j.jpeds.2016.05.080DOI Listing
November 2016

Bronchiolitis in young infants: is it a risk factor for recurrent wheezing in childhood?

World J Pediatr 2017 Feb 15;13(1):41-48. Epub 2016 Sep 15.

The Ruth and Bruce Rappaport School of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.

Background: Acute bronchiolitis in infancy is considered a risk factor for recurrent wheezing episodes in childhood. The present study assessed prevalence, clinical manifestations and risk factors for recurrent wheezing events during the first 3 years of life and persistent wheezing events beyond this age in children hospitalized as young infants with acute bronchiolitis.

Methods: Two groups of children aged 6 years were included. The study group comprised 150 children with a history of hospitalization for bronchiolitis, with the first event at <6 months of age. The control group comprised 66 age- and sex-matched children with no history of bronchiolitis before 6 months of age. Children in both groups had been followed until 6 years of age by their pediatricians; data were obtained retrospectively by reviewing ambulatory records during children's visits in pediatricians' clinics. The data included epidemiological parameters, prevalence, age at onset, number of and treatments given for episodes of wheezing events prior to 6 years of age, pathogens detected, and severity of acute bronchiolitis in the study group.

Results: Overall, 58% and 27% of children in the study and control groups, respectively (P=0.001) had recurrent wheezing episodes prior to the age of 3 years. Children in the study group had earlier onset of recurrent wheezing, had more episodes of wheezing, and required more bronchodilator and systemic steroids treatments compared to the control group.

Conclusion: Hospitalization within the first six months of life for acute bronchiolitis is an independent risk factor for recurrent wheezing episodes during the first 3 years of life.
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http://dx.doi.org/10.1007/s12519-016-0056-4DOI Listing
February 2017
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